TY - THES ID - 135145262 TI - Finding the genetic cause(s) of polymicrogyria in 22q11 deletion syndrome patients​ AU - Hannes, Laurens AU - Cleynen, Isabelle AU - Vermeesch, Joris AU - KU Leuven. Faculteit Geneeskunde. Opleiding Master in de geneeskunde (Leuven) PY - 2019 PB - Leuven KU Leuven. Faculteit Geneeskunde DB - UniCat UR - https://www.unicat.be/uniCat?func=search&query=sysid:135145262 AB - Polymicrogyria (PMG) and 22q11.2 deletion syndrome (22q11.2DS) have been linked for over 20 years. Pinpointing a genetic cause for this link has eluded us so far. We aimed to find this cause using a bottom up approach starting from 22q11.2DS patients afflicted with PMG through whole genome sequencing (WGS). Four genomes of patients with PMG and one with 22q11.2DS associated neurodevelopmental disorders were sequenced using NovaSeq (Illumina) and a WGS pipeline. Variants located in the deletion region were selected and annotated with gnomAD allele frequencies and several disease predicting scores. Applying cut-off values to these annotations allowed us to filter 8 potential disease-causing variants out of 425 unique rare variants found in our samples. We focussed on a gene PI4KA, previously linked to PMG. However, no conclusive evidence was found to strengthen this association. We found 149 unique variants not yet adopted in gnomAD. Surprisingly we observed heterozygous calls in this hemizygous region pointing to the presence of somatic mosaicism. Novel in silico methods aimed at annotating new intronic data provided by WGS could let us discover previously elusive connections between phenotypes and genotypes. However, the scarcity and novelty of available methods limits us in exploring and harnessing the vast amount of new and exciting data provided by WGS. ER -